A Phoenix-area research group will team with a Swiss pharmaceutical company to test two experimental drugs that aim to fend off Alzheimer's disease in older adults who are at high risk but have not yet shown memory or thinking problems.

The ambitious study will test the theory that Alzheimer's disease can be prevented or delayed with early treatment, much like cholesterol-lowering or blood-pressure medications that are used to reduce the risk of heart disease or stroke.

Novartis will offer two experimental drugs that will allow Phoenix-based scientists to evaluate different approaches to halt the disease in healthy individuals.

"This offers us two shots on goal," said Dr. Pierre Tariot, study director for Banner Alzheimer's Institute. "It's still an open question of which shot on goal will work best."

The institute in September secured a $33.2 million National Institutes of Health grant to underwrite a study that will seek to recruit more than 1,300 individuals who face great genetic risk of developing the disease later in life.

Banner Alzheimer's Foundation will contribute an additional $15 million in direct and in-kind support, and Novartis will contribute an undisclosed amount.

Banner Alzheimer's Institute and its research partners will test the effectiveness of two drugs, each with a slightly different approach of attacking the amyloid plaques that are found in the brains of Alzheimer's patients.

Amyloid is a protein that forms clumps of plaque in the brains of Alzheimer's patients. Scientists believe amyloid plaques scuttle memory and thinking and kill nerve cells, but there isn't scientific consensus whether these plaques trigger the disease or are a result of the disease.

While other drugs designed to remove plaque from patients' brains have failed, scientists believe those drugs were administered too late, after the disease had ravaged the brain. The Alzheimer's Prevention Initiative, led by Banner, will test the idea that amyloid plaque-busting drugs can halt or delay the disease if the patient gets them soon enough.

Alzheimer's is the sixth-leading cause of death in the United States and afflicts more than 5 million people in the country. That figure is expected to surge to 8 million in 2030.

The Banner-Novartis study will recruit more than 1,300 healthy individuals ages 60 to 75 who carry two copies of a gene, called APOE4, that puts them at greater genetic risk for developing Alzheimer's disease. Only 2 percent of the population inherits copies of the risk gene from both parents, but those individuals are more likely than not to develop Alzheimer's later.

Novartis will offer two of its experimental drugs as part of the trial. One drug, CAD106, is a vaccine designed to trigger the body's immune system to produce antibodies that attack amyloid.

The experimental drug already has been vetted in a early-stage clinical trial testing for its safety. Now, this trial could evaluate how well the vaccine works.

The second drug is a BACE inhibitor that is being tested in another early-stage trial to ensure it's safe to use in humans. The oral medication is designed to prevent the growth of the amyloid protein.

Michael Ryan, who oversees the Novartis unit that develops therapies for neurodegenerative diseases such as Alzheimer's, said the BACE inhibitor drug likely will not be available for the Banner study until 2016.

"Targeting amyloid as early as possible will give us the best shot" of developing an effective therapy for the disease, Ryan said.

Banner officials said studying both drugs simultaneously is an important part of the study. Although the final design has not been determined and is subject to regulatory approval, study participants are expected to get either the vaccine, the BACE inhibitor or a placebo.

The study is expected to include 60 centers across Europe and North America, including Banner Alzheimer's Institute in Phoenix.

MRI technologist Ann Nelson reviews an MRI scan for scan quality and further analysis by the research imaging team at the Banner Alzheimer's Institute in Phoenix, Monday, July 14, 2014. The scan is of the brain of a participant in a research study.(Photo: Tom Tingle, Tom Tingle/The Republic)

"We think that by studying these two drugs together, it's a much better test," said Dr. Eric Reiman, executive director of Banner Alzheimer's Institute.

The APOE4 study of late-onset Alzheimer's disease follows a related Banner study of a large Colombian family that carries a genetic mutation that virtually guarantees members will get Alzheimer's disease by their mid-40s.

The Colombians either receive crenezumab, made by the San Francisco Bay Area biotechnology company Genentech, or a placebo. The study includes a small group of Americans who have a genetic mutation that is a trigger for early-onset Alzheimer's. The study began last year, but no results have been publicly reported.

There are key differences in the two Alzheimer's studies. Although the Colombians are virtually guaranteed to get Alzheimer's disease, the Banner-Novartis trial will enroll individuals who are at risk but not guaranteed to develop Alzheimer's. Individuals who carry two copies of the APOE4 gene carry a 60 percent to 90 percent risk of developing the disease over their lifetime, Reiman said.

The Colombians are not informed of their genetic status, but the APOE4 carriers who agree to participate in the study will know they are carriers of the risk gene. All individuals who choose to participate in the trial — and are made aware of their genetic- test results — will be offered counseling.

Mark Rothstein, director of the University of Louisville's Institute for Bioethics, Health Policy and Law, said there are risks and potential benefits to conducting such as trial.

"A percentage of these people would never get Alzheimer's, and now, they are taking a drug to prevent it," Rothstein said. But he also said that such a trial may yield a breakthrough drug that potentially could benefit millions.

That's the hope of Reiman, who said the two studies illustrate his group's vision to attack Alzheimer's disease in its earliest stages.

"When we first proposed this idea five years ago, one could have viewed this idea as a bit quixotic and certainly a bit ambitious," Reiman said. "We believe the era of Alzheimer's prevention research has certainly arrived."

More information

Those who want more information about the Banner Alzheimer's Institute study can visit banneralz.org. Individuals who would like to volunteer for the Alzheimer's Prevention Registry can get more information at endalznow.org.

ON THE BEAT

Ken Alltucker covers health care for The Arizona Republic. He has written about the Affordable Care Act, consumer health, insurance, prescription drugs and hospitals.

How to reach him

ken.alltucker@arizonarepublic.com

Phone: 602-444-8285

Twitter: @kalltucker

Untangling Alzheimer's

To learn more about its causes, risk factors and treatments, plus dealing with dementia, read The Arizona Republic's series on